It is to be appreciated that any discussion of documents, devices, acts or knowledge in this specification is included to explain the context of the present invention. Further, the discussion throughout this specification comes about due to the realisation of the inventor and/or the identification of certain related art problems by the inventor. Moreover, any discussion of material such as documents, devices, acts or knowledge in this specification is included to explain the context of the invention in terms of the inventor's knowledge and experience and, accordingly, any such discussion should not be taken as an admission that any of the material forms part of the prior art base or the common general knowledge in the relevant art in Australia, or elsewhere, on or before the priority date of the disclosure and claims herein.
‘Wound healing’ is a general term for the process by which living skin tissue repairs itself in response to an injury. An injury triggers a complex set of overlapping biochemical events characterised by three main phases; (1) inflammation, (2) proliferation and (3) remodeling.
For example, within a few minutes of an injury to skin, platelets adhere to the injury site, become activated, and aggregate. The biochemical coagulation cascade is activated to form a clot of aggregated platelets enmeshed in cross-linked fibrin protein that stops active bleeding (hemostasis).
During the inflammation phase, neutrophils and macrophages phagocytose bacteria and cell debris, effectively removing them from the wound. During this phase platelet derived growth factors are released into the wound and cause the migration and division of cells during the proliferative phase.
During the proliferation phase, angiogenesis occurs and vascular endothelial cells form new blood vessels. Collagen deposition also occurs along with granular tissue formation, epithelialization, and wound contraction. In fibroplasia and granulation tissue formation, fibroblasts grow and form a new, provisional extracellular matrix by excreting collagen, fibronectin and other materials. Concurrently, re-epithelialization of the epidermis occurs, in which epithelial cells proliferate over the wound bed to cover the new tissue.
The wound contracts as myofibroblasts grip the wound edges and contract. When the cells' roles are complete, many become redundant and undergo apoptosis. During maturation and remodeling, collagen is remodeled and realigned along tension lines, and more redundant cells undergo apoptosis.
Skin tissue repair is thus a complex process and is susceptible to disruption, potentially resulting in the formation of non-healing chronic wounds. Factors that can contribute to non-healing chronic wounds include metabolic syndrome (diabetes, venous or arterial disease), infection, and metabolic deficiencies of old age.
Many different chemical moieties including trace elements such as selenium have been orally, or internally administered to a subject in attempts to improve wound healing. For example attempts have been made to show that selenium salt (in the form of sodium selenite) taken orally can accelerate wound healing in the diabetic condition—allegedly decreasing the expression of connexins and serum glucose in diabetic wounds as compared to non-diabetic wounds. In the diabetic wounds, the low levels of vascular endothelial growth factor and extracellular superoxide dismutase were restored to normal level following selenium administration and angiogenesis improved at the wound site (Baipai S et al, Biol Trace Elem Res. 2011 Ded; 144(1-3): 327-38. Epub 2011 Jun. 2). However the lack of rigorous statistical analysis of the results leaves the conclusions open to question. It is however apparent that the results are attributed to the antioxidant characteristic of the selenium salt. Interestingly, the results indicate that oral selenium salt administration appeared ineffective in accelerating wound healing in non-diabetic wounds.
In the past the consumption of selenium in health supplements and sports drinks has been associated with bolstering antioxidant defences and immune health, minimising the adverse effects of free radicals. For example, U.S. Pat. No. 4,668,515 describes a selenium-containing drink to maintain health and prevent the formation of spontaneous tumours of the mammary gland. DE 44 37 403 describes another antioxidant composition including bound selenium, also for internal administration. More specifically these treatments have been based on the antioxidant activity of such compounds.
Selenium compounds such as the water-soluble glutathione peroxidase (GPx) mimic DL-trans-3,4-dihydroxy-1-selenolane (DHSred) have been investigated for their potential to heal acute gastric ulcers induced by non-steroidal anti-inflammatory drugs (NSAID's). It is suggested that the healing action of DHSred in conjunction with omeprazole was due to antioxidant activity, ability to protect mucin and augmentation of prostaglandin synthesis. (Chakraborty S et al, Free Radical Research, 2012; 46(11) 1378-1386).
US 2011/0038956 (Kuklinski et al) teaches the use of selenite- or selenate-containing preparations supplemented with pharmaceutically acceptable acids for topical, buccal or mucosal administration to utilise the anti-oxidant activity of selenium to treat skin conditions caused by papillomavirus or mycoses and periodontal diseases such as stomatitis, aphthae or leucoplakia.
The use of the anti-oxidant activity of selenium containing compounds and their solubility in aqueous solutions such as plasma, is also taught and disclosed in WO 2012 054988 (U.S. Ser. No. 13/881,594). WO 2012/054988 identifies a group of seleno-compounds that regulate the presence of reactive oxygen species (ROS), such as hypohalous acids (e.g., HOCl and HOBr) and/or to minimise the adverse impact of such ROS by inhibiting or minimising the pathogenesis of certain conditions or disease states which are linked to tissue damage by ROS. More specifically the compounds comprise a stable seleno-moiety, which acts as a radical scavenger and in particular a scavenger of ROS or free-radicals derived from non-radical ROS and as such these compounds are able to function as antioxidants. Such compounds have significant potential in treating disorders linked to the effect of free radicals such as atherosclerosis, cystic fibrosis, sepsis, rheumatoid arthritis and other inflammatory disorders, some cancers, asthma, and cardiovascular diseases.